A nuclear cAMP microdomain suppresses tumor growth by Hippo pathway inactivation.
A nuclear cAMP microdomain suppresses tumor growth by Hippo pathway inactivation.
复制标题
DOI：
10.1016/j.celrep.2022.111412
复制
发表时间：
2022-09-27
期刊：
影响因子：
8.8
通讯作者：
Zippin, Jonathan H.
中科院分区：
文献类型：
--
作者：
Drozdz, Marek M.;Doane, Ashley S.;Alkallas, Rached;Desman, Garrett;Bareja, Rohan;Reilly, Michael;Bang, Jakyung;Yusupova, Maftuna;You, Jaewon;Eraslan, Zuhal;Wang, Jenny Z.;Verma, Akanksha;Aguirre, Kelsey;Kane, Elsbeth;Watson, Ian R.;Elemento, Olivier;Piskounova, Elena;Merghoub, Taha;Zippin, Jonathan H.
Cyclic AMP (cAMP) signaling is localized to multiple spatially distinct microdomains, but the role of cAMP microdomains in cancer cell biology is poorly understood. Here, we present a tunable genetic system that allows us to activate cAMP signaling in specific microdomains. We uncover a nuclear cAMP microdomain that activates a tumor-suppressive pathway in a broad range of cancers by inhibiting YAP, a key effector protein of the Hippo pathway, inside the nucleus. We show that nuclear cAMP induces a LATS-dependent pathway leading to phosphorylation of nuclear YAP solely at serine 397 and export of YAP from the nucleus with no change in YAP protein stability. Thus, nuclear cAMP inhibition of nuclear YAP is distinct from other known mechanisms of Hippo regulation. Pharmacologic targeting of specific cAMP microdomains remains an untapped therapeutic approach for cancer; thus, drugs directed at the nuclear cAMP microdomain may provide avenues for the treatment of cancer. Drozdz et al. develop a tunable genetic system allowing for the activation of cAMP sources in distinct organelles and subcellular domains. They discover that nuclear cAMP acts as a tumor suppressor in a wide range of human cancers through inactivation of the Hippo protein YAP inside the nucleus.
登录
查看更多内容
DOI：
10.1111/j.1600-0749.2006.00322.x
发表时间：
2006-08-01
期刊：
PIGMENT CELL RESEARCH
影响因子：
--
作者：
Hoek, Keith S.;Schlegel, Natalie C.;Dummer, Reinhard
通讯作者：
Dummer, Reinhard
影响因子：
5.3
作者：
DANG, CV;LEE, WMF
通讯作者：
LEE, WMF
影响因子：
64.8
作者：
Ghandi, Mahmoud;Huang, Franklin W.;Sellers, William R.
通讯作者：
Sellers, William R.
影响因子：
16.6
作者：
Franklin, J. Matthew;Ghosh, Rajarshi P.;Liphardt, Jan T.
通讯作者：
Liphardt, Jan T.
影响因子：
--
作者：
Magro, Cynthia M.;Crowson, A. Neil;Desman, Garrett;Zippin, Jonathan H.
通讯作者：
Zippin, Jonathan H.